miR-145 inhibits breast cancer cell growth through RTKN

Int J Oncol. 2009 May;34(5):1461-6.

Abstract

MicroRNAs (miRNAs) represent a class of small non-coding RNAs regulating gene expression by inducing RNA degradation or interfering with translation. Aberrant miRNA expression has been described for several human malignancies. Herein, we show that miR-145 is down-regulated in human cancer cell line MCF-7 when compared to normal human mammary epithelial cell line MCF10A. Overexpression of miR-145 by plasmid inhibits MCF-7 cell growth and induces apoptosis. Subsequently, RTKN is identified as a potential miR-145 target by bioinformatics. Using reporter constructs, we show that the RTKN 3' untranslated region (3'UTR) carries the directly binding site of miR-145. Additionally, overexpression of miR-145 in MCF-7 reduces RTKN protein expression as well as mRNA level. Furthermore, down-regulation of RTKN by siRNA can inhibit MCF-7 cell growth. Taken together, we propose that loss of miR-145 may provide a selective growth advantage for MCF-7 by targeting RTKN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Proliferation* / drug effects
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • GTP-Binding Proteins
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA, Small Interfering / pharmacology
  • Tumor Cells, Cultured

Substances

  • Apoptosis Regulatory Proteins
  • Intracellular Signaling Peptides and Proteins
  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • RTKN protein, human
  • GTP-Binding Proteins